Since Nerves of Cold Steel is useless to 2handed frost, you will be forced to take both Runic Power Mastery and Icy Reach. You can choose in the 2nd tier between Lichborne, Endless Winter, and On a Pale Horse.. You will pick up Might of the Frozen Wastes rather than Threat of Thassarian

Single Target Priority List:

Diseases > Obliterate when all frost and unholy runes are available or both death runes are up or if Killing Machine has procced > Blood Strike when both blood runes are up > Frost Strike > Rime > Obliterate > Blood Strike > Horn of Winter

Howling Blast will apply Frost Fever while you will need to Plague Strike to apply Blood Plague. Rime will easily keep Frost Fever up. You will need to Plague Strike through to refresh Blood Plague. This will leave you with one frost rune left. The best choice is to either let it sit or cast Howling Blast after the Plague Strike.

After diseases are up, check to see you're not sitting on two full runes of one type. Check that both pairs of runes for Obliterate are not up (all frost and unholy runes) and that both blood runes are not up (Blood Strike). If Killing Machine has procced and you are able to cast Obliterate, do so if you have a frost and unholy rune up. If you can't cast Obliterate with Killing Machine, then let Frost Strike take the Killing Machine proc (it is never worth delaying Frost Strike to save Killing Machine for an Obliterate that is not yet ready)

After that, simply move through your abilities. Cast Frost Strike if you can, if not then check to see if there is a Rime to burn off. After that try to use Obliterate then Blood Strike. If you have nothing else to do, then cast Horn of Winter.

Multiple Target:

This is considerably different than single target.

Howling Blast when both frost runes or both death runes are available > Death and Decay > Plague Strike when both Unholy Runes are available > Blood Strike if both Blood Runes are available > Frost Strike if Runic Power is at maxium > Howling Blast > Blood Strike > Death and Decay/Plague Strike > Frost Strike > Horn of Winter

Only use Pestilence to spread plague strike if the group is 10 mobs or greater, otherwise apply Blood Plague via tab-targeted Plague Strikes.

Glyphs

Single TargetPrime Glyph of Frost StrikeGlyph of Howling BlastGlyph of Obliterate